The present invention, in some embodiments thereof, relates to methods of monitoring and analyzing metabolic activity profiles and diagnostic or therapeutic uses of same, or specifically relates to cancer diagnosis by metabolic activity monitoring of blood samples.
A major problem in disease treatment remains early detection and staging. Early detection enables therapeutic treatment from the onset of the disease resulting in successful treatment in many cases. Staging of a disease might indicate on the appropriate protocol of medication which might be decisive for optimal treatment. For example today, millions of people are living with cancer or have had cancer. Cancer is the second most common cause of death in the United States, exceeded only by heart disease. Cancer accounts for nearly 1 out of every 4 deaths in the United States. The sooner a cancer is diagnosed and treated, the better the survival chances are.
All known methods for detection of cancer focus on identifying mostly the malignant tissue and/or its pathological cancer biomarkers secreted to the circulation. However, these diagnostic methods are only unfortunately effective at relatively advanced stages of the disease.
The Warburg effect is the observation that most cancer cells predominantly produce energy by a high rate of glycolysis followed by lactic acid production n in the cytosol, rather than by a comparatively low rate of glycolysis followed by oxidation of pyruvate in mitochondria like most normal cells [Kim J W, Dang C V (2006). “Cancer's molecular sweet tooth and the Warburg effect”. Cancer Res. 66 (18): 8927-30]. Second, in 1920s Otto Warburg found that cancer cells19,20, in contrast to normal differentiated cells, primarily rely on aerobic glycolysis rather than on mitochondrial oxidative phosphorylation to generate ATP as the fuel for energy needed for cellular processes. This historical phenomenon was termed “the Warburg effect”21. Otto Warburg postulated that this change in metabolism is the fundamental cause of cancer [Warburg O (1956). “On the origin of cancer cells”. Science 123 (3191): 309-14], a claim now known as the Warburg hypothesis. About 50 years later the Warburg effect was also observed in activated lymphocytes in vitro see e.g., Maclver et al. 2008 J. Leukocyte Biology 84:1-9; and DeBerardinis Cell Metabolism 7:11-20. The Warburg effect was found also in the immune system where activated T cells22,23 rapidly hyperinduce glycolysis, for example by over-expression of glucose transporters (GLUT)24.
The Warburg effect has important medical applications, as high aerobic glycolysis by malignant tumors is utilized clinically to diagnose and monitor treatment responses of cancers by imaging uptake of 2-18F-2-deoxyglucose (FDG) (a radioactive modified hexokinase substrate) with positron emission tomography (PET). See also WO2007/102146. However, these methods are cumbersome and expensive by requiring high-tech facilities or in-situ tissue biopsies.
Therefore, non-invasive methods for early and simple diagnosis are needed.